Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Acetaminophen toxicity in human lymphocytes in vitro

S P Spielberg

    The Journal of Pharmacology and Experimental Therapeutics
    |May 1, 1980
    PubMed
    Summary

    This study developed an in vitro method to assess acetaminophen toxicity using human lymphocytes. The system measures glutathione depletion and cell damage, potentially revealing individual differences in drug metabolism and toxicity susceptibility.

    Related Concept Videos

    You might also read

    Related Articles

    Articles linked to this work by shared authors, journal, and citation graph.

    Sort by
    Same author

    Further investigations of the role of acetylation in sulphonamide hypersensitivity reactions.

    Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals·2013
    Same author

    Clinical pharmacology: a discipline called to action for maternal and child health.

    Clinical pharmacology and therapeutics·2007
    Same author

    Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation.

    Journal of clinical pharmacology·2002
    Same author

    NASPGN and ESPGHAN on the use of cisapride.

    Journal of pediatric gastroenterology and nutrition·2000
    Same author

    Deficiency of cytosolic arylamine N-acetylation in the domestic cat and wild felids caused by the presence of a single NAT1-like gene.

    Pharmacogenetics·1999
    Same author

    Translational data gathering: how to apply adult dosing data to children.

    Inflammatory bowel diseases·1998

    Area of Science:

    • Pharmacology
    • Toxicology
    • Cell Biology

    Background:

    • Assessing individual drug toxicity susceptibility in humans is challenging due to limited noninvasive methods.
    • Acetaminophen (APAP) is a common drug with known toxicity risks.
    • Understanding individual differences in drug metabolism is crucial for personalized medicine.

    Purpose of the Study:

    • To develop and validate an in vitro system for assessing acetaminophen toxicity using human lymphocytes.
    • To investigate the role of glutathione depletion in acetaminophen-induced lymphocyte toxicity.
    • To explore the potential of this system for evaluating individual susceptibility to drug metabolite toxicity.

    Main Methods:

    • An in vitro system was established using human lymphocytes and mouse liver microsomes for acetaminophen metabolism.
    • Lymphocyte glutathione levels were measured following exposure to acetaminophen metabolites.
    • Cell viability was assessed using trypan blue exclusion, lactate dehydrogenase release, and concanavalin A response.

    Main Results:

    • Acetaminophen metabolites caused a dose-dependent depletion of lymphocyte glutathione.
    • Significant lymphocyte toxicity was observed at glutathione depletions exceeding 80%.
    • The observed toxicity levels correlated with in vivo acetaminophen-induced hepatotoxicity.

    Conclusions:

    • The developed in vitro system effectively models acetaminophen toxicity in human lymphocytes.
    • Glutathione depletion is a key indicator of acetaminophen-induced cellular damage.
    • This method offers a promising approach for assessing individual differences in susceptibility to drug toxicity.

    Related Experiment Videos